Professor Callender is interested in understanding how biologically important molecules function on a molecular level and has developed state-of-the-art spectroscopic techniques to obtain relevant structural, molecular, and kinetic information. Three broad problems are under investigation: the properties of visual pigments; the determination of structure and molecular properties of substrates bound to their enzymes; and how a large class of regulatory proteins, the so called G-proteins, work. In addition to these studies, measurements are now under way that determine the very early events, from picoseconds to milliseconds, of how proteins fold from a long polymer to their unique compact forms. Highlights of this year's progress are as follows. His laboratory has determined the catalytic mechanism of phosphoglucomutase, which catalyzes the hydrolysis of phosphate from glucose. This is the first such determination in any phosphate hydrolyzing enzyme, even though this is a very large and key class of enzymes. The ground state interactions of pyruvate and the NAD cofactors with lactate dehydrogenase have been quantitatively characterized, and related to its enzymic function. The binding characteristics of retinoids to a particular retinoid binding protein has been measured. Retinoid binding proteins are essential in many biochemical pathways, and little is known about how they bind selectively various retinoids. The unfolding of a 16 residue helical peptide induced by a temperature jump has been shown to be faster than one microsecond (which extends previous kinetic studies by three orders of magnitude).